1. Experimental model: Daily intra-peritoneal instillation of PD solution (Dianeal 3.86%) for 4-5 weeks via mini vascular access port (fig 1) Daily administration of COX-2 inhibitor (Celecoxib) (20mg/kg of body weight) diluted with PEG 95% via oral gavage On sacrifice day 90 min PET test with 30 ml Dianeal METHODS INTRODUCTION Peritoneal dialysis (PD) is associated with an inflammatory response of the peritoneal membrane, with new vessel formation, fibrosis, and loss of ultrafiltration capacity Cyclooxygenase-2(COX-2) is an inducible enzyme expressed in several tissues under pro-inflammatory stimuli. It regulates the production of prostaglandin involved in inflammation and angiogenesis process AIM of the study: investigated COX-2 inhibition effect on peritoneal morphological and functional changes induced by PD Fluid. COX-2 Inhibition Largely Prevents Peritoneal Worsening in Rat PD Model P Fabbrini 1, M Zareie 1, PM ter Wee 2, ED Keuning 1, RHJ Beelen 1, J van den Born 1 1 Dept. Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, Netherlands, 2 Dept. Nephrology,VU University medical Center, Amsterdam, Netherlands PEG 95% + CELECOXIB PEG 95% Oral treatment DIANEAL 3.86% NO Pd instillation 8+GROUP D+I 8+GROUP D 8-GROUP C+I 8-GROUP C nCatheter OMENTUM: ANGIOGENESIS -total number of blood vessel reduced to 50 % in group D+I vs D (p>0.01 ) -mast cell number reduced to 50 % in group D+I vs D (p>0.01 ) PARIETAL PERITONEUM: ANGIOGENESIS AND FIBROSIS - ANGIOGENESIS reduced to 40% in group D+I vs group D (p<0.05) Fig 3 Fig 3: parietal peritoneum stained with CD31ab, red spots (arrows )indicate blood vessels - FIBROSIS reduced to 40% in group D+I vs group D (p<0.05) PET TEST: CELL PARAMETERS - T otal number of cells do not significantly differ between D and D+I - No significant differences in cell subpopulation between D and D+I GROUPS BLOOD VESSELS/cm ECM thickness  m GROUPS a a a : p<0.05 vs D GROUPS BLOOD VESSEL/cm 2 MAST CELLS /cm 2 - No differences between UF capacity of D+I and C/C+I groups. GROUPS GROUP C GROUP C+I GROUP D GROUP D+I Fig 2: Omentum stained with toloudine blue; arrows indicate some blood vessels GROUP CGROUP C+IGROUP DGROUP D+I Total cell number 24.1 (13.1-26.9)19.1 (13.0-23.0)62.4 (26.2-182.5)a47.4 (21.4-114.1)a Macrophages80.0 (65.0-88.5)73.0 (57.0-78.0)b76.0 (55.0-82.5)69.5 (59.0-79.0)b Lymphocytes2.7 (0.0-5.0)3.0 (0.0-4.0)12.5 (7.0-25.0)a16.5 (16.0-34.0)a Neutrophils0.0 (0.0-0.0) 6.0 (3.0-10.5)a5.0 (2.0-15.0)a Eosinophils7.8 (5.5-14.0)10.0 (7.0-19.0)6.5 (1.0-18.0)2.5 (0.0-15.0) a Mastcells9.5 (0.5-10)15.0 (8.0-27.0)0.0 (0.0-1.5)a0.0 (0.0-1.0)a PET TEST: FUNCTIONAL PARAMETERS CONCLUSION Cox-2 downstream products have a major role in the peritoneal angiogenesis and fibrosis after exposure to PDF. Its suppression produced a generalized reduction of peritoneal damage in PDF exposed rats especially regarding omentum and parietal peritoneum Cox-2 suppression completely prevent the lost of peritoneal UF capacity observed in the PDF exposed control group RESULTS FIG 1 : a mini vascular acces port and a rat few days after implantation surgery Experimental groups: GROUP C GROUP C+I GROUP D GROUP D+I ULTRAFILTATION VOLUME ml a : p<0.05 vs C and C+I b : p <0.05 vs C a a : p<0.01 vs C ; C+I and D+I MESOTHELIAL CELLS ON LIVER: 213 (169-251)199 (135-211)1025 (56-121)*1055 (91-153)* C C+I D D+I * P<0.01 vs C and C+I -No differences in mesothelium regenerative response between group D and D+I